Tissues engineered in vitro can be used to restore and repair human tissues, potentially saving the lives of some patients waiting for organ donation. One major challenge in engineering complex tissues is directional control of cell movement. For example, different cell types assemble in specific patterns to form functional organs, capillaries sprout in the direction of new tissues or wounds, and neural cells migrate in specific directions during formation or regeneration of nervous systems. This proposed Exploratory/Development research investigates the feasibility of a completely novel approach for controlling the directional migration of cells using biodegradable scaffolds with micron-size patterns of asymmetrically shaped cell-adhesive islands. These specially shaped adhesive islands are designed to resemble combs having multiple sharp corners on one side and a smooth curved edge on the other. The basis of this design comes from previous studies with micropatterned cells, which demonstrated that single cells patterned on adhesive islands initiate lamellipodia extension - the first step of cell migration - preferentially at sharp corners of the cell periphery furthest from the cell nucleus. Cells patterned on these comb shaped islands are thus expected to extend lamellipodia preferentially from the side with multiple sharp corners. To demonstrate continuous coordination of cell migration, multiple comb-shaped islands are arranged in a circular pattern such that the sharp tips of the islands point towards the smoothly curved side of a neighboring island. The gaps between islands and between the pointed tips of the combs are set below the typical length of extended lamellipodia to allow cells to escape confinement and "hop" from one island to another in a predetermined counter-clockwise direction. A successful proof-of-principle demonstration of how cell shape, defined by the geometry of micropatterns, can be used to control the directional migration of cells on biomaterials will open many new avenues in the design of scaffolds for tissue engineering. These principles may be applied, for example, to control simultaneously the directional migration of endothelial (capillary) and hepatocyte (liver) cells into complex scaffold patterns similar to that found in liver tissues. This methodology can also be directly extended to form three-dimensional scaffolds either by cutting and twisting sheets of biomaterials or stacking multiple layers of these micropatterned sheets.